Advanced Research Institute (ARI): Supporting the Geriatric Mental Health Research Pipeline.

The Advanced Research Institute (ARI) in Mental Health and Aging is a NIMH-funded mentoring network to help transition early-career faculty to independent investigators and scientific leaders. Since 2004, ARI has enrolled 184 Scholars from 61 institutions across 34 states. We describe the ARI components and assess the impact and outcomes of ARI on research careers of participants. Outcomes of ARI graduates (n = 165) came from NIH Reporter, brief surveys, and CVs: 87.3% remained active researchers, 83.6% performed scientific service, and 80.6% obtained federal grants. A population-based analysis examined NIMH mentored K awardees initially funded from 2002-2018 (n = 1160): in this group, 77.1% (47/61) of ARI participants versus 49.5% (544/1099) of nonparticipants obtained an R01. Controlling for time, ARI participants were 3.2 times more likely to achieve R01 funding than nonparticipants. Given the struggle to reduce attrition from the research career pipeline, the effectiveness of ARI model could be relevant to other fields.

Fracture liaison service utilising an emergency department information system to identify patients effectively reduce re-fracture rate is cost-effective and cost saving in Western Australia.

OBJECTIVES: To assess the benefits of the Emergency Department Information System (EDIS)-linked fracture liaison service (FLS). METHODS: Patients identified through EDIS were invited to attend an FLS at the intervention hospital, the Sir Charles Gairdner Hospital (SCGS-FLS). The intervention group was compared to usual care. Retrospective control (RC) at this hospital determined historical fracture risk (SCGH-RC). Prospective control (PC) was from a comparator, Fremantle Hospital (FH-PC). The main outcome measures were cost-effectiveness from a health system perspective and quality of life by EuroQOL (EQ-5D). Bottom-up cost of medical care, against the cost of managing recurrent fracture (weighted basket), was determined from the literature and 2013/14 Australian Refined Diagnosis Related Groups (AR-DRG) prices. Mean incremental cost-effectiveness ratios were simulated from 5000 bootstrap iterations. Cost-effectiveness acceptability curves were generated. RESULTS: The SCGH-FLS program reduced absolute re-fracture rates versus control cohorts (9.2-10.2%), producing an estimated cost saving of AUD$750,168-AUD$810,400 per 1000 patient-years in the first year. Between-groups QALYs differed with worse outcomes in both control groups (p < 0.001). The SCGH-FLS compared with SCGH-RC and FH-PC had a mean incremental cost of $8721 (95% CI -$1218, $35,044) and $8974 (95% CI -$26,701, $69,929), respectively, per 1% reduction in 12-month recurrent fracture risk. The SCGH-FLS compared with SCGH-RC and FH-PC had a mean incremental cost of $292 (95% CI -$3588, $3380) and -$261 (95% CI -$1521, $471) per EQ-5D QALY gained at 12 months respectively. With societal willingness to pay of $16,000, recurrent fracture is reduced by 1% in >80% of patients. CONCLUSIONS: This simple and easy model of identification and intervention demonstrated efficacy in reducing rates of recurrent fracture and was cost-effective and potentially cost saving.

Time-course assessment of 3D-image distortion on the 1.5 T Marlin/Elekta Unity MR-LINAC.

PURPOSE: The efficacy of MR-guided radiotherapy on a MR-LINAC (MR-L) is dependent on the geometric accuracy of its MR images over clinically relevant Fields-of-View (FOVs). Our objectives were to: evaluate gradient non-linearity (GNL) on the Elekta Unity MR-L across time via 76 weekly measurements of 3D-distortion over concentrically larger diameter spherical volumes (DSVs); quantify distortion measurement error; and assess the temporal stability of spatial distortion using statistical process control (SPC). METHODS: MR-image distortion was assessed using a large-FOV 3D-phantom containing 1932 markers embedded in seven parallel plates, spaced 25 mm × 25 mm in- and 55 mm through-plane. Automatically analyzed T1 images yielded distortions in 200, 300, 400 and 500 mm concentric DSVs. Distortion measurement error was evaluated using median absolute difference analysis of imaging repeatability tests. RESULTS: Over the measurement period absolute time-averaged distortion varied between: dr = 0.30 - 0.49 mm, 0.53 - 0.80 mm, 1.0 - 1.4 mm and 2.28 - 2.37 mm, for DSVs 200, 300, 400 and 500 mm at the 98th percentile level. Repeatability tests showed that imaging/repositioning introduces negligible error: mean ≤ 0.02 mm (max ≤ 0.3 mm). SPC analysis showed image distortion was stable across all DSVs; however, noticeable changes in GNL were observed following servicing at the one-year mark. CONCLUSIONS: Image distortion on the MR-L is in the sub-millimeter range for DSVs ≤ 300 mm and stable across time, with SPC analysis indicating all measurements remain within control for each DSV.

Re-assessment of the climatic controls on the carbon and water fluxes of a boreal aspen forest over 1996-2016: Changing sensitivity to long-term climatic conditions.

Recent evidence suggests that the relationships between climate and boreal tree growth are generally non-stationary; however, it remains uncertain whether the relationships between climate and carbon (C) fluxes of boreal forests are stationary or have changed over recent decades. In this study, we used continuous eddy-covariance and microclimate data over 21 years (1996-2016) from a 100-year-old trembling aspen stand in central Saskatchewan, Canada to assess the relationships between climate and ecosystem C and water fluxes. Over the study period, the most striking climatic event was a severe, 3-year drought (2001-2003). Gross ecosystem production (GEP) showed larger interannual variability than ecosystem respiration (Re ) over 1996-2016, but Re was the dominant component contributing to the interannual variation in net ecosystem production (NEP) during post-drought years. The interannual variations in evapotranspiration (ET) and C fluxes were primarily driven by temperature and secondarily by water availability. Two-factor linear models combining precipitation and temperature performed well in explaining the interannual variation in C and water fluxes (R2 > .5). The temperature sensitivities of all three C fluxes (NEP, GEP and Re ) declined over the study period (p < .05), and, as a result, the phenological controls on annual NEP weakened. The decreasing temperature sensitivity of the C fluxes may reflect changes in forest structure, related to the over-maturity of the aspen stand at 100 years of age, and exacerbated by high tree mortality following the severe 2001-2003 drought. These results may provide an early warning signal of driver shift or even an abrupt status shift of aspen forest dynamics. They may also imply a universal weakening in the relationship between temperature and GEP as forests become over-mature, associated with the structural and compositional changes that accompany forest ageing.

Assessment of post-operative opioid prescribing practices in a community hospital ambulatory surgical center.

OBJECTIVE: To evaluate the prescribing practices and opioid consumption in an ambulatory setting to inform the development of evidence-based guidelines. DESIGN: A prospective study of adults undergoing outpatient open and laparoscopic surgeries over 3 months. One week after discharge, a telephonic interview quantified the number of opioids prescribed and consumed, degree of pain control and satisfaction, and whether additional pain medication was requested. SETTING: Community hospital ambulatory surgery center in Westchester County, New York. PARTICIPANTS: This study included 304 adults undergoing a variety of procedures by surgeons from multiple specialties. MAIN OUTCOME MEASURES: Quantify surgeons' postoperative opioid prescribing compared with patient opioid consumption. RESULTS: Eighty-one percent (N = 245) responded to the survey, of which 64 percent were prescribed opioids. Males and females were equally represented with the mean age of 59.4 years. Of those prescribed opioids, 92 percent filled the prescription. The most commonly prescribed opioids reported by the patients that filled their prescription (N = 145) were oxycodone (36.5 percent), oxycodone/acetaminophen (28.9 percent), and tramadol (22.7 percent). The mean number of opioid pills prescribed was 20 and the mean consumption was 6.7 pills, resulting in an average of 13 retained pills. Only 3.8 percent of the patients prescribed opioids at discharge called their provider for additional analgesia. Despite the low opioid consumption patients reported high satisfaction (4.5 on scale of 0-5) with pain control. Only 10.4 percent reported that the surgeon recommended an over the counter (OTC) analgesic option. There was variability in the amount of opioids prescribed within each surgical category. CONCLUSIONS: One week after outpatient surgery, patients consumed one-third of physician-prescribed opioids, yet they reported high pain management satisfaction. Our study will inform the development of a patient-centered interdisciplinary perioperative education program to more effectively tailor multimodal pain management in ambulatory surgical patients and collaterally reduce the number of retained opioids.

Interdisciplinary speed dating augments diabetes self-management education and support to improve health outcomes.

OBJECTIVE: To determine if a novel interdisciplinary "speed-dating" clinic augments Diabetes Self-Management Education and Support (DSMES). METHODS: Adult patients with diabetes attended a DSMES class. Two weeks later patients attended an interdisciplinary clinic utilizing a "speed-dating" format during which they progressed through 5 stations hosted by different healthcare disciplines at 30-minute increments: physician, pharmacist, nurse/dietitian, case manager, and psychologist. Shared decision-making was utilized to identify mutually agreeable recommendations. Change in clinical outcomes were compared for DSMES-only attenders versus Dual-attendees; utilization of emergency department and hospital services were measured 12 months before and after attending the Speed Dating clinic. This analysis represents patients attending the program during 2016. RESULTS: Sixty-nine attended the DSMES class, 40 of whom followed-up in the "speed-dating" clinic (58% return rate). Attending the Speed Dating clinic improved A1C (p = 0.003) and LDL-C (p = 0.003) compared to the DSMES class alone. Comparatively, after attending the speed-dating clinic, patients had fewer emergency department (p = 0.366) and hospital admissions (p = 0.036), and shorter lengths of hospital stay (p = 0.030). CONCLUSIONS: The interdisciplinary "speed-dating" approach improved diabetes outcomes beyond DSMES alone and reduced utilization of hospital services. PRACTICE IMPLICATIONS: Patients should attend DSMES but also participate in an Interdisciplinary Speed Dating follow-up to further improve outcomes.

Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY. MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process. RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1). CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.

Chronology of the Acheulean to Middle Stone Age transition in eastern Africa.

The origin of the Middle Stone Age (MSA) marks the transition from a highly persistent mode of stone toolmaking, the Acheulean, to a period of increasing technological innovation and cultural indicators associated with the evolution of Homo sapiens We used argon-40/argon-39 and uranium-series dating to calibrate the chronology of Acheulean and early MSA artifact-rich sedimentary deposits in the Olorgesailie basin, southern Kenya rift. We determined the age of late Acheulean tool assemblages from 615,000 to 499,000 years ago, after which a large technological and faunal transition occurred, with a definitive MSA lacking Acheulean elements beginning most likely by ~320,000 years ago, but at least by 305,000 years ago. These results establish the oldest repository of MSA artifacts in eastern Africa.

Evaluating the consistency of scales used in adult attention deficit hyperactivity disorder assessment of college-aged adults.

OBJECTIVE: Neurocognitive evaluations are commonly integrated with clinical assessment to evaluate adult Attention Deficit Hyperactivity Disorder (ADHD). Study goal is to identify measures most strongly related to ADHD diagnosis and to determine their utility in screening processes. PARTICIPANTS: 230 students who were evaluated at the Vanderbilt University Psychological and Counseling Center between July 2013 and October 2015. METHODS: We retrospectively examined charts, including clinical diagnosis, family history, childhood parental reported and current self-reported ADHD symptoms, psychiatric comorbidities, and continuous performance test (CPT). RESULT: Positive report of childhood and current ADHD symptoms, and lack of comorbid psychiatric symptoms were strongly associated with clinical diagnosis. CPT results were not associated with an ADHD diagnosis. The absence of reported childhood and current ADHD symptoms may serve as a contradictory marker for ADHD diagnosis. CONCLUSION: Clinical assessment of ADHD symptoms and ADHD childhood history, but not CPT, contributes to an accurate diagnosis of ADHD in college-aged adults.

Worth more than their weight in gold?

The cost of many topical prescription medications has increased in recent years. We have calculated that the cost per unit now exceeds that of many ?valuable' consumer items.

Building Resilience in an Urban Police Department.

OBJECTIVE: The aim of this study is to examine a resilience training intervention that impacts autonomic responses to stress and improves cardiovascular risk, psychological, and physiological outcomes in police. METHODS: Officers [(n = 38) 22 to 54 years] modified emotional and physical responses to stress using self-regulation. Measurements include psychological and physiological measures [eg, heart rate variability (HRV), blood pressure, C-reactive protein)] obtained at three time intervals. RESULTS: Age was significantly (P < 0.05) associated with changes on several measures of psychological stress (eg, critical incident stress, emotional vitality, and depression). Associations were found between coherence and improved HbA1c (r = -0.66, P < 0.001) and stress due to organizational pressures (r = -0.44, P = 0.03). Improvements in sympathetic and parasympathetic contributors of HRV were significant (P < 0.03). CONCLUSION: A stress-resilience intervention improves certain responses to job stress with greater benefits for younger participants.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system.

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf-tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: eaf-tip offset, leaf-tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C-series linac with a 120-leaf Millennium MLC, and validated the model using measured data. The leaf-tip offset is the geometric offset due to the rounded leaf-end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf-tip position, and tabulated data are available from the vendor. The leaf-tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at dmax in water. In-water profile comparisons were also used to verify the MLC leaf position (leaf-tip offset). The average transmission factor and leaf tongue-and-groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses (3 mm/3% and 2 mm/2%) were applied. In addition, computed output factors for MLC-defined small fields (2 × 2, 3 × 3, 4 × 4, 6× 6cm2) of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6MV and 18 MV models were both determined to have the same MLC parameters: leaf-tip offset = 0.3 cm, 2.5% transmission, and leaf tongue-and-groove width = 0.05 cm. IMRT QA analysis for five test cases in TG-119 resulted in a 100% passing rate with 3 mm/3% gamma analysis for 6 MV, and > 97.5% for 18 MV. The passing rate was > 94.6% for 6 MV and > 90.9% for 18 MV when the 2 mm/2% gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.

Out-of-pocket costs for childhood stroke: the impact of chronic illness on parents' pocketbooks.

OBJECTIVE: Direct costs for children who had stroke are similar to those for adults. There is no information regarding the out-of-pocket costs families encounter. We described the out-of-pocket costs families encountered in the first year after a child's ischemic stroke. METHODS: Twenty-two subjects were prospectively recruited at four centers in the United States and Canada in 2008 and 2009 as part of the "Validation of the Pediatric NIH Stroke Scale" study; families' indirect costs were tracked for 1 year. Every 3 months, parents reported hours they did not work, nonreimbursed costs for medical visits or other health care, and mileage. They provided estimates of annual income. We calculated total out-of-pocket costs in US dollars and reported costs as a proportion of annual income. RESULTS: Total median out-of-pocket cost for the year after an ischemic stroke was $4354 (range, $0-$28,666; interquartile range, $1008-$8245). Out-of-pocket costs were greatest in the first 3 months after the incident stroke, with the largest proportion because of lost wages, followed by transportation, and nonreimbursed health care. For the entire year, median costs represented 6.8% (range, 0%-81.9%; interquartile range, 2.7%-17.2%) of annual income. CONCLUSIONS: Out-of-pocket expenses are significant after a child's ischemic stroke. The median costs are noteworthy provided that the median American household had cash savings of $3650 at the time of the study. These results with previous reports of direct costs provide a more complete view of the overall costs to families and society. Childhood stroke creates an under-recognized cost to society because of decreased parental productivity.

Response assessment in locally advanced head and neck cancer based on RECIST and volume measurements using cone beam CT images.

The purpose of this work was to find potential trends in RECIST measurements and volume regressions obtained from weekly cone-beam computed tomography images and to evaluate their relationship to clinical outcomes in locally advanced head and neck cancer. We examined thirty head and neck cancer patients who underwent a pre-treatment planning CT and weekly cone-beam computed tomography (CBCT) during the 5-7 week treatment period. The gross tumor volume (GTV) and lymph nodes were manually contoured on the treatment planning CT. The regions of interest enclosed by delineated contours were converted to binary masks and warped to weekly CBCT images using the 3D deformation field obtained by deformable image registration. The RECIST diameters and volumes were measured from these warped masks. Different predictor variables based on these measurements were calculated and correlated with clinical outcomes, based on a clinical exam and a PET imaging study. We found that there was substantial regression of the gross tumor volume over the treatment course (average gross tumor volume regression of 25%). Among the gross tumor volume predicators, it was found that the early regression of gross tumor volume showed a marginal statistical significance (p = 0.045) with complete response and non-complete response treatment outcomes. RECIST diameter measurements during treatment varied very little and did not correlate with clinical outcomes. We concluded that regression of the gross tumor volume obtained from weekly CBCT images is a promising predictor of clinical outcomes for head and neck patients. A larger sample is needed to confirm its statistical significance.

Must an inventor "possess" an invention to patent it?

The requirements for patenting inventions relating to biotechnology have become increasingly strict and complicated in recent years. Despite early patent rulings that there is no need for an inventor to "reduce to practice" an invention, the courts are now ruling that an inventor must "possess" his or her invention before filing for patent. This review discusses what such "possession" may mean and describes decisions in which courts have found that an inventor has met or failed the possession test before filing for patent protection.

A general method for spatially coarse-graining Metropolis Monte Carlo simulations onto a lattice.

A recently introduced method for coarse-graining standard continuous Metropolis Monte Carlo simulations of atomic or molecular fluids onto a rigid lattice of variable scale [X. Liu, W. D. Seider, and T. Sinno, Phys. Rev. E 86, 026708 (2012)] is further analyzed and extended. The coarse-grained Metropolis Monte Carlo technique is demonstrated to be highly consistent with the underlying full-resolution problem using a series of detailed comparisons, including vapor-liquid equilibrium phase envelopes and spatial density distributions for the Lennard-Jones argon and simple point charge water models. In addition, the principal computational bottleneck associated with computing a coarse-grained interaction function for evolving particle positions on the discretized domain is addressed by the introduction of new closure approximations. In particular, it is shown that the coarse-grained potential, which is generally a function of temperature and coarse-graining level, can be computed at multiple temperatures and scales using a single set of free energy calculations. The computational performance of the method relative to standard Monte Carlo simulation is also discussed.

Lives saved by expanding HIV treatment availability in resource-limited settings: the example of Haiti.

BACKGROUND: Guidelines recommend antiretroviral therapy (ART) initiation at CD4 <350 cells per microliter for HIV-infected individuals in resource-limited settings. However, funding for treatment expansion remains uncertain. We forecast the mortality impact of ART expansion alternatives in Haiti. METHODS: We used data from Haiti to develop a country-specific model of HIV disease. The model projects the mortality, total number of HIV-infected individuals, and number and coverage (percentage of those eligible) on ART by simulating cohorts of HIV-infected individuals over 10 years. Five ART expansion scenarios, ranging from fully expanded ART (best case) to No New ART (worst case), were assessed. RESULTS: By 2010, the model predicts 103,500 individuals living with HIV in Haiti, of whom 27,300 were estimated to receive ART. Continuing ART initiation at current rates requires increasing the number on ART to 43,300 by 2020 (56% coverage), with 89,700 deaths estimated between 2010 and 2020. The number on ART could increase by 7400 (+17.1%, best case) or decrease by 25,600 (-59.1%, worst case), resulting in 19,500 deaths averted and 9900 fewer in care awaiting ART (best versus worst case). Results are sensitive to untreated disease progression and pre-ART loss from care. Increased HIV testing, linkage to care, and retention in care can avert additional deaths and achieve nearly 80% ART coverage with optimal policy improvements. CONCLUSIONS: In resource-limited settings, continued improvements in HIV treatment access will save lives. Efforts to efficiently expand ART access should remain a global priority.